Platelet membrane coated nanoparticles and uses thereof

Abstract

The present disclosure provides for platelet membrane coated nanoparticles that comprise, inter alia, an immunomodulating agent that is a toll-like receptor (TLR) agonist and/or an upregulator of the opioid growth factor receptor. Compositions, e.g., medicament delivery devices and pharmaceutical compositions, comprising the present nanoparticles are also provided. Uses of the present nanoparticles, including uses of the present nanoparticles for treating or preventing a neoplasm in a subject, are further provided.

1 . A nanoparticle, which comprises: 
 a) an inner core comprising a non-cellular material;   b) an outer surface comprising a cellular membrane derived from a platelet; and   c) an immunomodulating agent that is a toll-like receptor (TLR) agonist and/or an upregulator of the opioid growth factor receptor.   
     
     
         2 . The nanoparticle of  claim 1 , wherein the inner core comprises a polymer. 
     
     
         3 - 9 . (canceled) 
     
     
         10 . The nanoparticle of  claim 1 , wherein the inner core comprises a biocompatible or a synthetic material selected from the group consisting of poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polylysine, and polyglutamic acid. 
     
     
         11 . The nanoparticle of  claim 1 , wherein the cellular membrane comprises a plasma membrane derived from a platelet. 
     
     
         12 - 16 . (canceled) 
     
     
         17 . The nanoparticle of  claim 1 , wherein the immunomodulating agent is a toll-like receptor (TLR) agonist. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . The nanoparticle of  claim 1 , wherein the immunomodulating agent is resiquimod, imiquimod, or motolimod. 
     
     
         21 - 25 . (canceled) 
     
     
         26 . The nanoparticle of  claim 1 , wherein the inner core supports said outer surface. 
     
     
         27 - 38 . (canceled) 
     
     
         39 . A process for making a nanoparticle comprising:
 a) contacting an immunomodulating agent that is a toll-like receptor (TLR) agonist and/or an upregulator of the opioid growth factor receptor with a polymer to form an organic phase in an organic solvent;   b) contacting said organic phase with an aqueous phase to form a primary emulsion;   c) subjecting said primary emulsion to sonication or a high pressure homogenization to form a fine emulsion;   d) removing said organic solvent from said fine emulsion to form a nanoparticle comprising said immunomodulating agent and said polymer in said fine emulsion; and   e) recovering said nanoparticle from said fine emulsion.   
     
     
         40 - 69 . (canceled) 
     
     
         70 . A method for treating or preventing a neoplasm in a subject in need comprising administering to said subject an effective amount of a nanoparticle of  claim 1 . 
     
     
         71 - 74 . (canceled) 
     
     
         75 . The method of  claim 70 , wherein the subject is a human. 
     
     
         76 . The method of  claim 70 , wherein the immunomodulating agent is a toll-like receptor (TLR) agonist or an upregulator of the opioid growth factor receptor. 
     
     
         77 . The method of  claim 70 , wherein the immunomodulating agent is resiquimod, imiquimod, or motolimod. 
     
     
         78 . (canceled) 
     
     
         79 . The method of  claim 70 , wherein the neoplasm is a lymphoma, a leukemia, a brain cancer, glioma/glioblastoma (GBM), a multiple myeloma, a pancreatic cancer, a liver cancer, a stomach cancer, a breast cancer, a kidney cancer, a lung cancer, non-small cell lung cancer (NSCLC), a colorectal cancer, a colon cancer, a prostate cancer, an ovarian cancer, a cervical cancer, a skin cancer, an esophageal cancer, or a head and neck cancer. 
     
     
         80 . The method of  claim 70 , wherein the neoplasm is a solid cancer or tumor. 
     
     
         81 - 82 . (canceled) 
     
     
         83 . The method of  claim 70 , wherein the nanoparticle, medicament delivery or pharmaceutical composition is administered intratumorally or in situ to a solid cancer or tumor site in a subject. 
     
     
         84 . (canceled) 
     
     
         85 . The method of  claim 70 , wherein the nanoparticle, medicament delivery or pharmaceutical composition is administered to a subject in combination with another anti-neoplastic agent or substance, e.g., doxycycline. 
     
     
         86 . (canceled) 
     
     
         87 . The method of  claim 70 , wherein the nanoparticle, medicament delivery or pharmaceutical composition is administered to a subject that has been treated with anti-neoplastic agent or substance, e.g., doxycycline. 
     
     
         88 . (canceled) 
     
     
         89 . The method of  claim 70 , wherein the nanoparticle, medicament delivery or pharmaceutical composition is administered to a subject as a first line of treatment. 
     
     
         90 . The method of  claim 70 , wherein the nanoparticle, medicament delivery or pharmaceutical composition is administered to a subject with relapse neoplasm, e.g., a relapse solid cancer or tumor. 
     
     
         91 . (canceled) 
     
     
         92 . The method of  claim 70 , which achieves a survival rate of at least about 80% in the treated subjects for at least about three months.